| Title: | Revisiting the genetic support of leukotriene pathway drug targets in atherosclerotic cardiovascular disease |
| Journal: | Frontiers in Genetics |
| Published: | 14 Oct 2026 |
| DOI: | https://doi.org/10.3389/fgene.2026.1812905 |
| URL: | https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2026.1812905/pdf |
Publication 21524
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Abstract
Arachidonate 5-lipoxygenase (5-LO) and its activating protein, encoded by ALOX5 and ALOX5AP respectively, are two leukotriene pathway proteins suspected to play a role in atherosclerotic cardiovascular disease (ASCVD) through inflammatory mechanisms. Prior genetic association studies linking ALOX5 and ALOX5AP to ASCVD have motivated clinical trials of 5-LO inhibitors, such as atreleuton, which was associated with reduced atherosclerotic plaque progression in patients with a recent acute coronary syndrome in a phase II trial. However, the effect of 5-LO inhibition on ASCVD clinical outcomes remains unclear. Using data from the UK Biobank, we revisit previously reported genetic associations of ALOX5 and ALOX5AP with ASCVD using a multi-ancestry meta-analysis including data from 378,962 participants. We characterize ancestral differences in previously studied ALOX5 and ALOX5AP polymorphisms which could have led to population stratification. When adequately accounting for ancestry, these previous associations were not replicated. In addition to our replication efforts, we used association scans and transcriptome-wide association studies to test the involvement of leukotriene pathway genes with ASCVD. Overall, our results do not support a role for genetic variation in ALOX5 or its activating protein in ASCVD risk.</p>
4 Authors
- Tristan St-Laurent
- Julien St-Pierre
- Julien Quang Le Van
- Marc-André Legault
1 Application
| Application ID | Title |
|---|---|
| 89052 | Developing and applying advanced statistical methods to dissect genetic and genomic heterogeneity in diverse complex traits |
Enabling scientific discoveries that improve human health